Pre-eclampsia is a pregnancy-specific disorder associated with hypertension and proteinuria, characterized by alterations in endothelial cell function. In the present study we have compared responses to the endothelium-dependent vasodilator, bradykinin, in small myometrial arteries from normal pregnant and non-pregnant women and women with pre-eclampsia, in order to assess the relative contributions of nitric oxide, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in mediating endothelium-dependent vasodilatation. Bradykinin-induced concentration-dependent relaxation in arteries isolated from the three subject groups did not differ with regard to sensitivity or maximum response. Responses to bradykinin in all three groups were unaffected by cyclo-oxygenase inhibition alone, and were similarly unaffected by partial depolarization. The nitric oxide synthase (NOS) inhibitor, N-nitro-l-arginine methyl ester, significantly attenuated the responses to bradykinin in arteries from non-pregnant women and almost abolished responses in arteries from women with pre-eclampsia. However, in arteries from normal pregnant women, bradykinin-induced responses were maintained in the presence of NOS inhibition. Inhibition of NOS combined with partial depolarization abolished responses to bradykinin in these vessels. These results support the suggestion that, in the absence of NO, an EDHF can mediate vasodilator responses to bradykinin during normal pregnancy, an effect not apparent in arteries from non-pregnant women or women with pre-eclampsia. The up-regulation of EDHF-type function may represent a vascular adaptation to normal pregnancy that is absent in pre-eclampsia, and this might contribute to the clinical features of the disease.
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Research Article|
June 11 2002
Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia
Louise C. KENNY;
Louise C. KENNY
1
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2RW, U.K.
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Philip N. BAKER;
Philip N. BAKER
1
†School of Human Development, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2RW, U.K.
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David A. KENDALL;
David A. KENDALL
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2RW, U.K.
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Michael D. RANDALL;
Michael D. RANDALL
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2RW, U.K.
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William R. DUNN
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2RW, U.K.
Correspondence: Dr William R. Dunn (e-mail [email protected]).
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Publisher: Portland Press Ltd
Accepted:
March 27 2001
Received:
December 04 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 103 (1): 67–73.
Article history
Accepted:
March 27 2001
Received:
December 04 2001
Citation
Louise C. KENNY, Philip N. BAKER, David A. KENDALL, Michael D. RANDALL, William R. DUNN; Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia. Clin Sci (Lond) 1 July 2002; 103 (1): 67–73. doi: https://doi.org/10.1042/cs1030067
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